Adding mesenchymal stem cells to coils may promote biological healing, providing a definitive cure for aneurysms that can be delivered endovascularly, according to a preclinical study published online this month in the Journal of NeuroInterventional Surgery.
“The problem in the endovascular treatment of aneurysm is . . . risk of recanalization,” lead author Aymeric Rouchaud, MD (Mayo Clinic, Rochester, MN), told Neurovascular Exchange in an interview. “In about 30% of cases, there will be a recurrence. This is a problem for patients because it means the need for second-[line] treatment.”
Current devices, he explained, just “mechanically occlude the aneurysms. We hope with stem cells to have biological healing of the aneurysms and reconstruct a new artery at the neck of the aneurysm so there is no remnant.”
Rouchaud and colleagues created aneurysms in a rabbit model. In six rabbits, they embolized the aneurysms using control platinum coils. In another seven, they first seeded the coils ex vivo with autologous adipose-tissue mesenchymal stem cells. Aneurysm neck size, width, and height were similar for both groups. Packing density was greater in the experimental group, with an interquartile ratio (IQR) of 30.0% vs 22.5% in the control group (P = 0.01.
Rouchaud explained to NVX that this study builds on previous research in which mesenchymal stem cells were infused into aneurysms, also in a rabbit model. They found that deposit rates at the aneurysmal site were not high enough, so they decided to seed coils in an effort to improve it.
In the current study, 1-month aneurysmal occlusion rates after embolization, evaluated using angiography, revealed a greater rate of stable or progressive occlusion with the stem cell treatment compared with controls (0.00; 95% CI 0.00-0.41 vs 0.67; 95% CI 0.22-0.96; P = 0.02).
Histological examination revealed a greater healing score, degree of fibrosis (defined as the ratio of the total area presenting collagen), and endothelialization of the neck among models treated with stem cells, compared with controls.
Histological Outcomes of Aneurysm Repair With and Without Mesenchymal Stem Cells
|
|
With (n = 7) |
Without (n= 6) |
P Value |
|
Healing Score |
11.5 |
8.0 |
0.019 |
|
Fibrosis Ratio |
10.3 |
0.13 |
0.006 |
|
Endothelialization, μm2 |
902,262 |
31,810 |
0.041 |
In addition, aneurysms treated with seeded coils showed marked cellular proliferation and thrombus organization, with a continuous membrane bridging the neck of the aneurysm.
A ‘First Step’ Toward Definitive Therapy
“This is a first step and shows that biological healing [may be] the way to go for definitive treatment of aneurysms,” said Rouchaud.
The next step in their research, he added, will be to confirm the safety of the procedure before moving on to human trials, but he has high hopes. “In rabbits, we saw no risks for using stem cells in the aneurysms, and there was a great potential for healing,” Rouchaud reported. “So, hopefully we can [move] quite fast to human [trials]. Stem cells are already used for other indications, like for hematological disease. There are also some trials going on in acute stroke.”
He noted that the risks were likely low because they used autologous stem cells, so there is little or no risk of rejection of the graft. They also anticipate that attachment of the stem cells to coils reduces or eliminates the risk of cell mobilization, which can lead to ischemic issues from embolization.
The team is currently working towards collecting enough data to obtain permission to conduct trials in human subjects.
Source:
Rouchaud A, Brinjikji W, Dai D, et al. Autologous adipose-derived mesenchymal stem cells improve healing of coiled experimental saccular aneurysms: an angiographic and histopathological study. J NeuroInterv Surg. 2018;Epub ahead of print.
Disclosures:
Rouchaud reports no relevant conflicts of interest.
